Dose response effects of postnatal hydrocortisone on growth and growth factors in the neonatal rat

Area of Science:

• Neonatal Medicine
• Endocrinology
• Developmental Neuroscience

Background:

• Hydrocortisone (HC) is used in critically ill newborns for lung and blood pressure support.
• Long-term effects of early HC exposure on postnatal growth are not well understood.
• This study investigated the persistent effects of early high-dose HC on growth, metabolism, and neurological outcomes.

Purpose of the Study:

• To determine if early high-dose hydrocortisone exposure adversely affects postnatal growth, growth factors, metabolic hormones, and neurological outcomes.
• To assess if these effects persist into adulthood.
• To evaluate the dose-dependent impact of hydrocortisone on developmental trajectories.

Main Methods:

• Rat pups received daily intramuscular doses of hydrocortisone (1, 5, or 10 mg/kg) or saline on postnatal days 3-5.
• Body weight, linear growth, and neurological function were monitored.
• Hormone levels, liver gene expression, and cognitive function (Morris water maze) were assessed at various time points up to P70.

Main Results:

• High-dose HC suppressed body weight and length in early life, with catch-up overgrowth by P70 in some groups.
• Adult rats exposed to high HC doses exhibited low insulin, IGF-I, GH, and leptin, but high blood glucose and liver IGFs/IGFBPs.
• Delayed memory and learning abilities were observed in high-dose HC groups at P70.

Conclusions:

• Early high-dose hydrocortisone administration can lead to significant long-term deficits in growth, metabolism, and neurocognitive function.
• These findings highlight potential adverse consequences of neonatal hydrocortisone therapy that persist into adulthood.
• Careful consideration of HC dosage is crucial to balance immediate clinical benefits with potential long-term developmental risks.